The present invention relates to a novel method for treatment of HIV infection by using an extract from inflammatory tissue inoculated with vaccinia virus. More particularly, it relates to a combined therapy for HIV infection with anti-HIV drugs and the extract.
Acquired Immunodeficiency Syndrome (AIDS) is a disease caused by infection of Human Immunodeficiency Virus (HIV), one species of lentivirus, which induces a progressive decrease in immune function leading ultimately to death. At present in the United States (as of August 2003), eight nucleoside/nucleotide reverse transcriptase inhibitors, three non-nucleoside reverse transcriptase inhibitors, seven protease inhibitors, and one fusion inhibitor are approved as anti-HIV chemotherapeutic drugs. A therapy using a combination of these drugs, named highly active antiretroviral therapy (HAART), is commonly used and standardized.
HAART can suppress the replication of HIV in an infected patient and can prevent the progress of HIV infection. However, it is necessary to suppress the replication of HIV completely for several decades to prevent the development of AIDS. The discontinuation of the chemotherapy at any time following injection causes a rebound in, and repopulation of, HIV. Thus, a patient is required to receive the chemotherapy continuously during most of his or her lifetime. It is difficult to take anti-HIV drugs continuously because anti-HIV drugs have a large formulation. As a result, many drugs must be taken at each dosage. Further, the anti-HIV drugs induce various and strong side effects. If a patient does not keep the dosage schedule very strictly, the treatment meets with failure by the induction of a drug-resistant virus.
As mentioned above, the continuous use of anti-HIV drugs for a long period of time in HIV infected patients, while keeping a consistent dosage schedule of almost 100%, has caused various problems, including the decrease of quality of life (QOL) for patients, economic burdens, and risk of long term toxicity. To avoid these problems, it is desirable to provide an alternative to continuous treatment of HIV-1 infected patients with conventional FDA approved anti-HIV chemotherapeutic drug regimens.
The pharmacological activities of an extract from an inflammatory tissue inoculated with vaccinia virus include: (1) analgesic, sedative, anti-stress and anti-allergic effects (Japanese Patent Laid-Open No. Sho-53-101515); (2) immuno-enhancing, anti-cancer and hepatocirrhosis suppressive effects (Japanese Patent Laid-Open No. Sho-55-87724); (3) therapeutic effect for idiopathic thrombocytopenic purpra (Japanese Patent Laid-Open No. Hei-1-265028); (4) therapeutic effects for post-herpetic neuralgia, brain edema, dementia, and spiro-cerebellar degeneration purpra (Japanese Patent Laid-Open No. Hei-1-319422, U.S. Pat. No. 5,013,558); (5) therapeutic effects for Raynaud syndrome, diabetic neuropathy, and sequelae of myelo-optico neuropathy (Japanese Patent Laid-Open No. Hei-2-28119); (6) inhibitory effect on kallikrein production and improving effect of peripheral circulatory disturbance (Japanese Patent Laid-Open No. Hei-7-97336, U.S. Pat. No. 5,560,935); (7) improving effect of bone atrophy (Japanese Patent-Laid-Open No. Hei-8-291077); (8) suppressive effect of nitrogen monoxide useful for therapy of sepsis and endotoxin shock (Japanese Patent Laid-Open No. Hei-10-194978, U.S. Pat. No. 6,051,613); (9) therapeutic effect for osteoporosis (Japanese Patent Laid-Open No. Hei-11-80005); (10) therapeutic effect for AIDS by Nef action inhibiting effect or chemokine-production increasing effect (Japanese Patent Laid-Open No. Hei-11-139977 or 2000-336034); (11) therapeutic effect for ischemic diseases such as cerebral infarction (Japanese Patent Laid-Open No. 2000-16942); and (12) therapeutic effect for fibromyalgia (International PCT Publication No. WO2004/039383).
An aspect of the present invention is to provide a method for treatment of HIV infection to offer an alternative to the problems associated with the long term use of anti-HIV drugs, such as the decrease of QOL of patients accompanied with therapy for HIV infection including AIDS, economical burdens, strong side effects of anti-retroviral drugs, and appearance of drug-resistant viruses. In particular, the present invention provides a novel adjunct method for the treatment of HIV to give persisting effectiveness to suppress HIV replication.
The present inventors have conducted various studies regarding the suppression on HIV replication for the therapy of HIV infection. As a result, the inventors found that after viral loads are lowered by the administrations of an approved anti-HIV drug, the suppressive action on HIV replication can be maintained by the administration of an extract from inflammatory tissue inoculated with vaccinia virus, during a time period during which the conventional anti-HIV drugs are terminated.